The goal of the proposed 5-year epidemiologic study is to assess the impact of Mexico's new drug laws on behaviors and disease incidence among injection drug users (IDUs) in the U.S. In August, 2009, Mexico enacted a controversial law decriminalizing possession of personal-sized quantities of drugs including heroin, cocaine, methamphetamine and cannabis. The sister-cities of San Diego, CA, USA and Tijuana, BC, Mexico share the world's busiest land border crossing and are home to nearly 4 million residents. Through research collaborations with the University of California, San Diego and partners in Tijuana, we found: i) increasing drug use and HIV prevalence in Tijuana;ii) dramatically higher prevalence of hepatitis C virus (HCV) and M. tuberculosis (Mtb) infections among IDUs in Tijuana versus San Diego;and, iii) injecting in Mexico reported by 21% of IDUs in San Diego. "Drug tourism" to Mexico among San Diegan IDUs may be an unintended consequence of Mexico's relaxed drug laws and could increase their risk for HCV, Mtb and HIV infections. This epidemiologic study aims to: 1) identify sociodemographic, behavioral, and health status differences between IDUs in San Diego who do and do not inject in Mexico;2) describe changes in San Diegan IDUs'knowledge, attitudes, and experiences related to Mexican drug policies and assess their influences on decisions about injecting in Mexico;and 3) determine whether San Diegan IDUs who inject in Mexico are at increased risk for incident HCV and Mtb infection and identify risk factors for infection. To achieve these aims, we will use a mixed-methods design involving quantitative and qualitative data collection. Quantitative methods include recruiting a cohort of 750 IDUs in San Diego via respondent driven sampling for semi-annual behavioral assessments and serologic testing for HIV, HCV, and Mtb infections over 24 months of follow-up. HIV and HCV antibody testing will be performed on serum using standard practices;Mtb infection will be detected by QuantiFERON TB-Gold assay. Qualitative methods involve selecting 20 participants after each assessment visit (total=100) for in-depth interviews that will be used to: i) explore novel findings that emerge in preliminary analysis of the quantitative data;ii) identify new areas of inquiry for addition to the quantitative assessments;and iii) assess the validity of quantitative findings by presenting them for interpretation to study participants in qualitative interviews. The iterative process of using qualitative and quantitative data to inform methods and interpret findings of each approach facilitates a comprehensive understanding of the conceptual model describing how Mexico's new law will impact the behaviors and health outcomes of IDUs in San Diego. This study meets NIDA priorities supporting epidemiologic research on HIV/AIDS co-morbidities including HCV and tuberculosis, and the prevention of HIV among vulnerable populations. This study exploits a rare natural experiment to evaluate the impact of opposing drug policies on interconnected, bordering communities, and will provide important insights for future policies. PUBLIC HEALTH RELEVANCE: Injection drug users (IDUs) are disproportionately affected by HIV, hepatitis C, and tuberculosis, and, the recently recognized convergence of these diseases in Tijuana, Mexico-sister city to San Diego, CA- suggests that progression of disease and rates of transmission will increase without effective interventions. In August, 2010 Mexico enacted new legislation decriminalizing possession of personal-size quantities of narcotic drugs (e.g., methamphetamine, heroin, cocaine, and cannabis), which it is feared will encourage more U.S. IDUs to visit Mexico to buy and use drugs. In parallel with a NIDA-funded study that will assess the law's impact on IDUs in Tijuana, we will conduct a longitudinal cohort study to examine the law's impact on the behaviors and disease risks among IDUs in San Diego who can readily cross the border to and from Mexico.